ABSTRACT: Background: The risk of cardiovascular (CV) diseases associated with aging is increasing as individuals with Down syndrome (DS) are living longer. CV disease risk factors diagnosed in children track into adulthood and cause dementia and heart attacks. Because many CV disease risk factors are modifiable, however, early treatment may delay or prevent adult disease. Subclinical changes in vascular health can be measured using vascular studies, including pulse wave velocity (PWV), carotid intimal medial thickness (CIMT), and carotid distensibility (CD). Each measure has been associated with future risk of vascular disease. Data in adults with DS show CV disease risk factor profiles and vascular study results differ compared to results from individuals without DS. In children with DS, CV disease risk factor data are limited with few studies evaluating the impact of CV disease risk factors on vascular health. We aim to determine the prevalence of CV disease risk factors in children with DS and evaluate their effect on vascular markers of early atherosclerosis. Research Design and Methods: We propose a cross-sectional evaluation of CV disease risk factors and their impact on vascular health in children with DS to be performed at 3 centers within the Pediatric Heart Network (PHN). Specific Aim 1: Evaluate CV disease risk factors in children with DS. We will describe common CV disease risk factors in children with DS including anthropometric measures, clinical risk factors (diet; activity; smoke exposure; hypertension; history of congenital heart disease, sleep apnea, cancer; and family history of early CV disease), and serologic risk factors (fasting lipid profiles with sub-fractionation, insulin, glucose, hemoglobin AIc, and CRP) in children with DS. We will compare these data to published national norms of children without DS. Specific Aim 2: Determine the associations between CV disease risk factors and markers of early atherosclerosis in children with DS. We will perform PWV, CIMT, and CD studies in children with DS and compare these data to available data in children without DS. We will use findings from Specific Aim 1 to perform multivariable analysis to determine the influence of combinations of vascular disease risk factors unique to children with DS on their vascular studies. Career Development Plan: The KL2 Career Development Award will address these gaps in my current research abilities: 1) improve my understanding and ability to evaluate CV risk factors, prediction models, and outcome measures including those used in interventional trials; 2) ability to perform and interpret advanced vascular imaging studies; 3) develop the expertise in study design, statistics, epidemiology, and research leadership needed to conduct CV studies in children with DS. These weaknesses will be addressed using the resources provided by the University of Utah's robust KL2 program and through recommended courses and hands-on training as well as interactions with an international team of mentors and advisors.